The term "plasma" refers to the soluble fluid portion of blood including organic substances, such as proteins, fats, sugars and other organic compounds, and inorganic substances, such as minerals. The term "plasma" does not include particulate components suchh as blood cells.
Blood is composed of a number of different components. Approximately 45% of the volume is composed of cellular matter, including red cells (erythrocytes), while cells (leukocytes) and platelets, all of which are much larger in size than plasma components. Plasma is the fluid that suspends the cellular materials and makes up the remaining 55%. It consists of approximately 90% water, 7% protein, which includes antibodies, antigens, immune complexes, pathogens, toxins, and other molecules, and 3% of various other organic and inorganic matter.
The term "plasmapheresis" is commonly defined as the removal of whole blood from the body, separation of its cellular elements by centrifugation, and reinfusion of cellular elements suspended in saline or some other plasma substitute, thus depleting the body's own plasma protein without depleting its cells (Stedman's Medical Dictionary, 24th Ed., 1982). Where treatment of the plasma and its return to the body, rather than its permanent removal, is desired, blood is withdrawn from the patient, the plasma is separated, treated, admixed with an appropriate volume of replacement fluid, and subsequently returned to the body. This technique is useful for treatment of various disease states, as discussed more fully below.
Plasma collection from donors is desirable for use in medical settings where a victim has lost large amounts of body fluids which need to be replenished. A bank or stored collection of plasma is a valuable asset to hospitals, especially those which have trauma centers or major surgery facilities. Treatment of the donor plasma to remove pathogens such as immune deficiency virus ("HIV") which causes Acquired Immune Deficiency Syndrome ("AIDS") is growing ever more important with the epidemic rise of AIDS and the increasing concern for the world's blood and plasma supply. Plasmapheresis can also be used as a diagnostic tool to detect disease-causing substances in the blood by analyzing the plasma fraction. This is especially valuable where a particular test or assay encounters interfering reactions from cellular components.
Removal of pathogenic material from a patient's blood is believed to benefit patients; e.g., removal of immune complexes is believed to be useful in the treatment of certain cancers. Numerous other conditions may possibly be treated using plasmapheresis including, but not limited to, myasthenia gravis, glomerulonephritis, Goodpasture's syndrome, pemiphigus, herpes gestationis, severe asthma; certain immune complex diseases such as crescentic nephritis, systemic lupus erythematosus, diabetic hypertriglyceridemia, hypercholesterolemia, macroglobulinemia, Waldenstrom's syndrome, hyperviscosity syndromes, paraproteinemias, myeloma, Raynaud's disease and phenomenon, thrombocytopenia, renal transplantation, rhesus incompatibility; poisons such as paraquat; Factor VIII inhibitor or antibodies, hepatic coma, preparation of immunoglobulins, human tetanus immunoglobulin, and the like.
A typical plasmapheresis system comprises a means for removing whole blood from a vein. The vein is used rather than an artery because of the high arterial pressure and surge within the vessel. Venous pressure is more constant, thereby providiing a more convenient source of blood. The whole blood is then delivered outside the body, or "extracorporeally," to a means for separating plasma from cellular components. The separated plasma is then delivered to a means for filtering, dialyzing or otherwise treating the plasma to remove undersirable components. In some cases desirable substances may be added to the plasma. If necessary, a volume of replacement fluid can be added to the plasma. The treated plasma is then reinfused into the patient. In the typical system, the plasmapheretic separation of plasma and cellular components occurs extracorporeally, after whole blood has been removed from the body. The separation is commonly done by centrifugation.
Unfortunately, typical plasmapheresis techniques can cause damage to the blood cells by subjecting them to severe shearing stresses or high pressurization which causes an interaction between the cells and the device surfaces where damage occurs to the cell membrane, and pieces of the cell are removed causing hemolysis. Moreover extracorporeal separation of blood cells increases the possibility of infection or contamination from the mechanical apparatus, technician error, environmental conditions or other sources. As centrifugation requires additional machinery to perform the separation, expensive bulky apparatus is necessary, adding to the system (and patient's) cost. Similarly, extracorporeal membrane filtration of blood increases the chance of contamination with infectious agents.
U.S. Pat. No. Re. 31,688 issued to Popovitch et al., discloses a method and apparatus for continuous plasmapheresis whereby whole blood is withdrawn from the body and separated by continuously ultrafiltering the patient's blood at specified shear stresses and membranes employing a membrane ultrafilter. The apparatus delivers whole blood for extracorporeal separation as compared to in vivo separation. The problems of contamination and damage to the red and white blood cells are present. The ultrafiltration chamber used in that invention adds additional mechanism and the use of bulky machinery prevents and ambulatory concept from being employed.
A problem in the prior art is that the plasmapheresis apparatus is largge and difficult to trasport. Because of this limitation, a patient with a chronic problem, such as a non-functioning kidney, must be treated periodically by travelling to an appropriate yet sometimes distant facility. Typically, the kidney patient will be treated when the toxic substances in the blood reach high levels. Thus, the typical kidney patient will cycle between low levels of toxic substances immediately after dialysis to high levels of toxic substances immediately before dialysis. This cycling of toxic substances is harmful to other organs in the body.
A plasma separation method and apparatus is needed that is small and easily transportable. In addition, the plasma separation method and apparatus should be continuous in operation so that the concentration of toxic substances will not build up, but can be continuously removed. Further, such plasma separation method and apparatus should reduce the manipulations that must be performed extracorporeally thereby reducing the opportunity for infection.